Triple negative breast cancer and non-small cell lung cancer: Clinical challenges and nano-formulation approaches

Ghosh, Saikat; Javia, Ankit; Shetty, Saritha; Bardoliwala, Denish; Maiti, Kuntal; Banerjee, Subhasis; Khopade, A. J.; Misra, Ambikanandan; Sawant, Krutika; Bhowmick, Subhas

doi:10.1016/j.jconrel.2021.07.014

Cited by 62 publications

(32 citation statements)

References 287 publications

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“…However, efficiency of dox treatment is limited due to low plasma solubility, poor blood pharmacokinetics, and non-selective cell killing, resulting in serious toxicity to healthy tissues, such as cardiac muscle [14]. In addition to these detrimental side effects, cancer cells exposed to doxorubicin often develop doxorubicin resistance [15]. Therefore, novel drug delivery systems to overcome drug resistance and off-target side effects are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Circumventing Doxorubicin Resistance Using Elastin-like Polypeptide Biopolymer-Mediated Drug Delivery

Dragojevic

Turner

Raucher

2022

IJMS

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Although doxorubicin (dox), an anthracycline antibiotic, is widely used and effective in treating cancer, its treatment efficiency is limited by low blood plasma solubility, poor pharmacokinetics, and adverse side effects, including irreversible cardiotoxicity. Moreover, cancer cells often develop drug resistance over time, which decreases the efficacy of anti-cancer drugs, including dox. In this study, we examine a macromolecular drug delivery system for its ability to specifically deliver doxorubicin to cancer cells with and without drug resistance. This drug delivery system consists of a multi-part macromolecule, which includes the following: elastin-like polypeptide (ELP), cell penetrating peptide (CPP), a cleavable linker (releasing at low pH), and a derivative of doxorubicin. ELP is thermally responsive and improves drug solubility, while the CPP mediates cellular uptake of macromolecules. We compared cytotoxicity of two doxorubicin derivatives, where one is cleavable (DOXO) and contains a pH-sensitive linker and releases dox in an acidic environment, and the other is non-cleavable (ncDox) doxorubicin. Cytotoxicity, apoptosis, cell cycle distribution and mechanism of action of these constructs were tested and compared between dox-responsive MCF-7 and dox-resistant NCI/ADR cell lines. Dox delivered by the ELP construct is comparably toxic to both sensitive and drug resistant cell lines, compared to unconjugated doxorubicin, and given the pharmacokinetic and targeting benefits conveyed by conjugation to ELP, these biopolymers have potential to overcome dox resistance in vivo.

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Section: Introductionmentioning

confidence: 99%

Circumventing Doxorubicin Resistance Using Elastin-like Polypeptide Biopolymer-Mediated Drug Delivery

Dragojevic

Turner

Raucher

2022

IJMS

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“…The 5-year survival rate of lung cancer after diagnosis was approximately 10–20% during 2010–2014 [ 27 ]. Intravenous injection of taxane-based chemotherapeutics remains the most frequently employed regimen for NSCLC treatment [ 29 , 30 ]. However, intravenously administered taxane can cause severe side effects and is rapidly metabolized, greatly reducing the quality of life of patients [ 1 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Biomimetic and temporal-controlled nanocarriers with ileum transporter targeting for achieving oral administration of chemotherapeutic drugs

et al. 2022

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Background Oral chemotherapy is preferred for patients with cancer owing to its multiple advantages, including convenience, better patient compliance, and improved safety. Nevertheless, various physical barriers exist in this route that hamper the development of oral chemotherapeutic formulations, including destruction of drugs in the gastrointestinal tract (GIT), low permeability in enterocytes, and short residence time in the intestine. To overcome these limitations, it is necessary to design an efficient oral drug delivery system with high efficacy and improved safety. Results Herein, we designed novel glycocholic acid (GCA)-functionalized double layer nanoparticles (GCA-NPs), which can act via an endogenous pathway and in a temporally controlled manner in the intestine, to enhance the oral bioavailability of hydrophobic chemotherapeutic drugs such as paclitaxel (PTX). GCA-NPs were composed of quercetin (Qu)-modified liposomes (QL) coated with GCA-chitosan oligosaccharide conjugate (GCOS). The GCA-NPs thus prepared showed prolonged intestinal retention time and good GIT stability due to the presence of chitosan oligosaccharide (COS) and enhanced active transportation via intestinal apical sodium-dependent bile acid transporter (ASBT) due to the presence of GCA. GCA-NPs also efficiently inhibited intestinal P-gp induced by Qu. PTX-loaded GCA-NPs (PTX@GCA-NPs) had a particle size of 84 nm and an entrapment efficiency of 98% with good stability. As a result, the oral bioavailability of PTX was increased 19-fold compared to that of oral Taxol® at the same dose. Oral PTX@GCA-NPs displayed superior antitumor efficacy and better safety than Taxol® when administered intravenously. Conclusions Our novel drug delivery system showed remarkable efficacy in overcoming multiple limitations and is a promising carrier for oral delivery of multiple drugs, which addresses several challenges in oral delivery in the clinical context. Graphical Abstract

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“…TNBC belongs to the most aggressive subtype of breast cancer, always accompanying worse clinical outcome (Feng Wang et al, 2021). Despite improvement in breast cancer therapeutic measures, the treatment for TNBC clinically without obvious side effects is still a huge challenge (Ghosh et al, 2021). Searching for complementary and alternative medicine is critical for the advancement of current TNBC therapies.…”

Section: Discussionmentioning

confidence: 99%

Maackiain Modulates miR-374a/GADD45A Axis to Inhibit Triple-Negative Breast Cancer Initiation and Progression

et al. 2022

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Breast cancer ranks as the leading cause of death in lethal malignancies among women worldwide, with a sharp increase of incidence since 2008. Triple negative breast cancer (TNBC) gives rise to the largest proportion in breast cancer-related deaths because of its aggressive growth and rapid metastasis. Hence, searching for promising targets and innovative approaches is indispensable for the TNBC treatment. Maackiain (MA), a natural compound with multiple biological activities, could be isolated from different Chinese herbs, such as Spatholobus suberectus and Sophora flavescens. It was the first time to report the anti-cancer effect of MA in TNBC. MA could suppress TNBC cell proliferation, foci formation, migration, and invasion. MA also exerted a significant inhibitory effect on tumor growth of TNBC. Furthermore, MA could induce apoptosis with an increase of GADD45α and a decrease of miR-374a. In contrast, overexpressing miR-374a would result in at least partly affecting the proapoptotic effect of MA and suppressing GADD45α stimulated by MA. These results reveal the anti-TNBC effect of MA in vitro and in vivo, providing evidence for its potential as a drug candidate utilized in TNBC therapy.

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Triple negative breast cancer and non-small cell lung cancer: Clinical challenges and nano-formulation approaches

Cited by 62 publications

References 287 publications

Circumventing Doxorubicin Resistance Using Elastin-like Polypeptide Biopolymer-Mediated Drug Delivery

Circumventing Doxorubicin Resistance Using Elastin-like Polypeptide Biopolymer-Mediated Drug Delivery

Biomimetic and temporal-controlled nanocarriers with ileum transporter targeting for achieving oral administration of chemotherapeutic drugs

Maackiain Modulates miR-374a/GADD45A Axis to Inhibit Triple-Negative Breast Cancer Initiation and Progression

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